Cyanomethanodioxocins and carboxymethanodioxocins



United States Patent 3,532,718 CYANOMETHANODIOXOCINS ANDCARBOXYMETHANODIOXOCINS Chun-Shan Wang, Midland, and Henry E. Hennis,Coleman, Mich., assignors to The Dow Chemical Company, Midland, Mich., acorporation of Delaware No Drawing. Filed Mar. 25, 1968, Ser. No.715,486 Int. Cl. C07d 7/24 US. Cl. 260-345.2 12 Claims ABSTRACT OF THEDISCLOSURE New cyanomethanodioxocins and carboxymethanodioxocins havingthe formula Where each of x and y independently is an integer of from 0to 4 inclusive; Ar is a homocyclic or heterocyclic substituted orunsubstituted ring; R is H; R is H, alkyl or aryl; R and R may togetherwith the C to which they are attached form the cyclohexane ring, R is H,alkyl or aryl; and R is cyano or carboxyl, are made from theircorresponding bromomethanodioxocins. The cyanodioxocins are usefulstarting materials for plasticizers and resins. Thecarboxymethanodioxocins have biological activity and are startingmaterials for plasticizers and resins.

CROSS-REFERENCE TO RELATED APPLICATIONS These new cyanodioxocins andcarboxymethanodioxocins are related to the bromomethanodioxocins asdisclosed in the application filed by one of us, Hennis, entitledMethanodioxocins and a Process for Making Them, Ser. No. 669,694, filedSept. 22, 1967.

SUMMARY OF THE INVENTION It has now been found that newcyanomethanodioxocins and carboxymethanodioxocins are made from theircorresponding bromomethanodioxocins. These new methanodioxocins have theformula Where each of v w, x and y independently is an integer of from 0to 4 inclusive; each of A, B, E, F, G, J, K and L independently is N orCH provided that neither A and E, E and G, G and K, B and F, F and I nor.T and L can simultaneously be N; R is H; R is H, alkyl having up toeighteen carbon atoms or aryl having up to ten carbon atoms; R and R maytogether with the C to which they are attached form the cyclohexanering; R is H, alkyl having up to eighteen carbon atoms or aryl having upto ten carbon atoms; each of R R R and R being absent when theircorresponding subscript v, w, x or y is 0, when present is independentlyalkyl hav ing up to eighteen carbon atoms, aryl having up to ten carbonatoms, chlorine, cyano, carboxyl or OM where M is a hydrocarbon radicalhaving up to eighteen carbon atoms provided that at least one of R R Rand R is always cyano or carboxyl and further provided that in no casecan a cyano and carboxyl group be present in the same molecule; and Rcombined with R as well as R combined with R together with the atoms towhich they are attached, may form the pyridine, pyrimidine, quinoline,benzene, naphthalene, anthracene, phenanthrene or pyran ring. An exampleof a specific new cyanodioxocin is 2-cyano-6H,12H-6,l2-methanodibenzo[b,f] [1,5 ]dioxocin, or a shorter term, 2-cyano-MDBD 13CH2 9 9 LCN COOHIn order to produce the new cyanodioxocins, a bromodioxocincorresponding to the cyanodioxocin desired is contacted with cuprouscyanide in the presence of an inert solvent, e.g. pyridine, at atemperature between and 200 C. wherein the molar ratio of cuprouscyanide to bromine on the dioxocin ring system is at least one to one.After reaction, the solvent is removed from the crude cyanodioxocin byconventional methods, e.g. distillation, and the crude cyanodioxocin isheated under Weakly acidic conditions, e.g. 10 percent hydrochloric acidand dissolved in and recrystallized from a suitable solvent, e.g.acetone, to yield the pure product.

In order to produce the new carboxydioxocins, a bromodioxocincorresponding to the carboxydioxocin desired is contacted with lithiummetal or an alkyllithium compound, e.g. n-butyl lithium in the presenceof an inert solvent, e.g. a benzene and ether mixture. This mixture isheated under a nitrogen atmosphere and maintained at a temperature ofbetween 30 and 100 C. The reaction mixture is then poured onto solid COand water is then added to form two layers. Acidification of the waterlayer with hydrochloric acid yields the desired carboxydioxocin which ispurified by recrystallization from an appropriate solvent, e.g.tetrahydrofuran.

The bromodioxocin starting materials are prepared from the reaction ofan appropriate o-vinylhydroxy aromatic compound with an appropriateo-hydroxyaldehyde aromatic compound as is more fully set forth inMethanodioxocins and aProcess for Making Them, Ser. No. 609,694, filedSept. 22, 1967, the disclosure of which is hereby incorporated byreference. A specific bromodioxocin, 2-bromo-MDBD is made by thereaction of o-coumaric acid 5-bromosalicylaldehyde, water andhydrobromic acid. After heating the above mixture at reflux temperaturefor 16 hours, sodium hydroxide is added and the resulting mixture isheated at reflux temperature for an additional hour. After filtration,the yellow solid remaining is 2-bromo-MD'BD. Other bromodioxocins aremade by selection of appropriate aromatic reactants as is shown in theabove cited application.

The cyanodioxocins are useful starting materials for their correspondingcarboxydioxocins which in turn are starting materials for plasticizersand resins. For example, the cyanodioxocins are readily converted totheir corresponding carboxydioxocins by well known hydrolysis conditionsin the presence of an acid or a base. Specifically, 70% sulfuric acid oraqueous sodium hydroxide easily converts a cyanodioxocin to itscorresponding carboxydioxocin.

The carboxydioxocins are useful as starting materials for plasticizersand resins. For example, both the mono and polycarboxylic derivatives ofMDBD are made into plasticizers by reaction with alcohols, e.g. octylalcohol, to make esters which have low vapor pressure and are diflicultto leach out. The low vapor pressure gives the plastic material a longuseful life before it becomes brittle and cracks. The polycarboxylicacids are made into useful resins by heating with polyamines, e.g. adiamine such as hexamethylenedianiine at about 250 C., to make a usefulpolyamide suitable for fibers and castings. Similarly, they can be madeinto polyester resins by esterification with an alcohol, e.g. methanol,followed by a transesterification reaction with ethylene glycol. Inaddition, they are useful bacteriocides.

DESCRIPTION OF SPECIFIC EMBODIMENT Example 1 for c qHmNgog 74.45; H,3.65; N, 10.22. Found (percent): C, 74.50; H,

Example 2 2-cyano-MDBD.-The same procedure and amount of reactants asthe preparation of 2,8-dicyano-MDBD was adopted except that 2-bromo-MDBDwas used in place of 2,8-dibromo-MDBD. The melting point of the Whiteneedle product was 153-155" C.

Analysis.Calcd. for C H NO (percent): C, 77.10; H, 4.41; N, 5.62. Found(percent): C, 76.9; H, 4.31; N, 5.99.

Example 3 2,8-dicarboxy-MDBD.To a solution of 9 g. of 2,8- dibromo-MDBDin 100 ml. of benzene was added 21 g. of a 15% solution of n-BuLi inether. The reaction was conducted under a nitrogen atmosphere. Heatingwas started as soon as n-BuLi solution was added to the solution andafter a short time, white solid started to precipitate out. In thecourse of an hour at 5060 C., the solution was full of whiteprecipitate. Then the reaction mixture was poured into crushed solid COwith stirring. Ether (100 ml.) was used to wash out the slurry remainingin the flask. After 0.5 hour, water was added and two layers formed.Acidification of the water layer with hydrochloric acid gave a whitesolid. The ether layer was 4 extracted with 10% sodium bicarbonatesolution. Acidification of the bicarbonate solution gave small amountsof white solid. The combined white solids were recrystallized from thetetrahydrofuran to give 4.6 g. (63%) of white solids, M.P. 300.

Analysis.-Calcd. for C H O (percent): C, 65.38; H, 3.85. Found(percent): C, 65.60; H, 4.03.

This chemical was dissolved in isopropanol and diluted to 500 parts permillion in warm melted agar. After solidification of the agar solution,a droplet containing Bacillus subrilis was placed on its surface andincubated. 50% control of Bacillus subtilis was observed.

This acid can be heated with excess n-octyl alcohol and toluene atreflux temperature in the presence of catalytic amounts ofp-toluenesulfuric acid. Water formed by the esterification reaction isremoved by azeotropic distillation with toluene. The organic solutioncan then be extracted with 5% sodium bicarbonate solution to remove anyunreacted acid and the catalyst. The clear viscous residue is then mixedwith polyvinyl chloride to give flexibility to the plastic.

Example 4 2-carboxy-MDBD.The same procedure and amount of reactants asthe preparation of MDBD-2,8-dicarboxylic acid was used except that2-bromo-MDBD was used in place of 2,8-dibromo-MDBD. The melting point ofthe white solid product was 179-1 82 C.

Analysis.Calcd. for C H O (percent): C, 71.34; H, 4.48. Found (percent)C, 70.8; H, 4.49.

Some other new cyanodioxocins which are produced from theircorresponding bromodioxocins by similar methods are:

4-cyano-MDBD or 4-carboxy-MDBD from 4-br0mo- MDBD;

1-cyano-MDBD or l-carboxy-MDBD from l-bromo- MDBD;

3-cyano-MDBD or 3-carboxy-MDBD from 3-brorno- MDBD;

2,4-dicyano-MDBD or 2,4-dicarboxy-MDBD from 2, 4-dibromo-MDBD.

1,3-dicyano-MDBD or 1,3 dicarboxy-MDBD from 1,3-dibromo-MDBD;

7,9 dicyano-MDBD or 7,9-dicarboxy-MDBD from 7,9-dibromo-MDBD;

2,4,8,l0-tetracyano MDBD or 2,4,8,10-tetracarboxy- MDBD from2,4,8,l0-tetrabromo-MDBD;

3-cyan0-13-methylMDBD or 3 carboxy-13-methyl- MDBD from3-bromo-13-methyl-MDBD;

6-ethyl-8-cyano-13-methyl-MDBD or 6 ethyl-8-carboxy-13-methyl-MDBD from6-ethyl-8-bromo-13-methyl- MDBD;

Z-methyl-lO-cyano-MDBD or 2 methyl-IO-carboxy- MDBD from2-methyl-10-bromo-MDBD;

6-cyano-8,15-dimethyl-MBDBD or 6-carboxy-8,15-di methyl MBDBD from6-bromo-8,l5-dimethy1-MBDBD;

2-chloro-10-cyano MDBD or 2 chloro-lO-carboxy- MDBD from2-chloro-10-bromo-MDBD;

6,11 dimethyl 9 cyano-7H,13H-7,13-methano-(1,5)-benzodioxocino(3,4-c)-quinoline or 6,11 dimethyl-9- carboxy7H,13H-7,13 methano(1,5)-benzodioxocino(3,4-c)-quinoline from 6,11dimethyl-9-brorno-7H, 13H 7,13 methano(1,5) benzodioxocino(3,4 c)-quinoline;

6-ethyl 8 cyano 13 methyl-6H,l2H-6,12-methano (1,5 )-benzodioxocino(3,4b) pyridine or 6 ethyl-8- carboxy l3 methyl-6H,12H-6,12-methan0( 1,5)-benzodioxocino(3,4-b) pyridine from 6 ethyl-8-bromo 13- methyl-6H,12H6,12 methano(1,5) benzodioxocino (3,4-b)pyridine;

Z-methoxy 4 cyano MDBD or Z-methoxy 4 carboxy-MDBD from Z-methoxy 4bromo MDBD; and

l-chloro 2 cyano-MDBD or 1 chloro-2-carb0xy MDBD from1-chloro-2-bromo-MDBD.

Similarly, the cyanodioxocins and carboxydioxocins given in Table Ibelow are made from their corresponding bromodioxocins.

further provided that in no case can a cyano and carboxyl group bepresent in the same molecule; and R combined with R, as well as Rcombined with R together with TABLE I A L 3)v i 2- J (R5) (mfi) cn R $301 y o F K O CH B R1 R2 R3 R4 R5 R6 Rad-R4 R Ru A B E F G J K L C 111CmHga m CH CH O C CH C CH CH CaHn Phenoxy C C CH C C H C H C H C CmHaaC3H1 OCmHga CH CH C CH CH C C CH Ihenyl CH C 119 O CH C CH C CH N C CCH3 C4H9 C CH C N CH CH C CH C4 0 Phenyl CH O 0 CH CH C C C CH C N ns azC4Ho Nnphthoxy O C O O CH N C H CH C 3 7 C1s 37 CiaHm A CH CH C C CH CHN CH is ai 04H C Ho CH C N CH CH CH C C 4m e m /k 3) OH N o o o 0 CH 0 Nph hyl CmHss CH3 OCwHga N CH C C C CH CH CH 1 Cyano or carb oxyl.

2 Naphthyl.

We claim: the atoms to which they are attached may form the hen- 1. Acompound having the formula where each of v, w, x and y independently isan integer of from 0 to 4 inclusive; R is H; R is H, alkyl having up toeighteen carbon atoms or aryl hydrocarbon having up to ten carbon atoms;R and R may together with the C to which they are attached form thecyclohexane ring; R is H, alkyl having up to eighteen carbon atoms oraryl hydrocarbon having up to ten carbon atoms; each of R R R and Rbeing absent when their corresponding subscript v, w, x or y is 0, whenpresent is independently alkyl having up to eighteen carbon atoms, arylhydrocarbon having up to ten carbon atoms, chlorine, cyano, carboxyl or0M where M is an alkyl radical having up to eighteen carbon atoms orphenyl, provided that at least one of R R R and R is always cyano orcarboxyl and zene, naphthalene, anthracene or phenanthrene ring.

2. A compound as defined in claim 1 wherein R R R and R are in the 2, 4,8 and 10 positions.

3. A compound as defined in claim 1 wherein R and R are in the 2 and 8positions and R and R are H.

4. A compound as defined in claim 1 wherein R is H or alkyl having up toeighteen carbon atoms.

5. A compound as defined in claim 1 wherein R and R are H.

6. A compound as defined in claim 1 wherein R is H or alkyl having up toeighteen carbon atoms.

7. A compound as defined in claim 1 wherein any ring formed by thecombination of R and R is the benzene, naphthalene, anthracene orphenanthrene ring.

8. A compound as defined in claim 1 wherein any ring formed by thecombination of R and R is the benzene, naphthalene, anthracene orphenanthrene ring.

9. Z-cyano-MDBD having the formula 7 10. 2,8-dicyano-MDBD having theformula 11. 2-carboxy-MDBD having the formula 8 12. 2,8-dicarboxy-MDBDhaving the formula HOOC- 011-0 CH2 OOOH O CH References Cited Bhatia etaL, Tetrahedron Letters, pp. 1717-20 (1966).

15 US. Cl. X.R.

